PMID- 21115832
OWN - NLM
STAT- MEDLINE
DCOM- 20110512
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 50
DP  - 2010 Dec 14
TI  - Identification of 9-cis-retinoic acid as a pancreas-specific autacoid that 
      attenuates glucose-stimulated insulin secretion.
PG  - 21884-9
LID - 10.1073/pnas.1008859107 [doi]
AB  - The all-trans-retinoic acid (atRA) isomer, 9-cis-retinoic acid (9cRA), activates 
      retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in vitro. RARs 
      control multiple genes, whereas RXRs serve as partners for RARs and other nuclear 
      receptors that regulate metabolism. Physiological function has not been 
      determined for 9cRA, because it has not been detected in serum or multiple 
      tissues with analytically validated assays. Here, we identify 9cRA in mouse 
      pancreas by liquid chromatography/tandem mass spectrometry (LC/MS/MS), and show 
      that 9cRA decreases with feeding and after glucose dosing and varies inversely 
      with serum insulin. 9cRA reduces glucose-stimulated insulin secretion (GSIS) in 
      mouse islets and in the rat beta-cell line 832/13 within 15 min by reducing glucose 
      transporter type 2 (Glut2) and glucokinase (GK) activities. 9cRA also reduces 
      Pdx-1 and HNF4alpha mRNA expression,  approximately 8- and 80-fold, respectively: defects in Pdx-1 
      or HNF4alpha cause maturity onset diabetes of the young (MODY4 and 1, respectively), 
      as does a defective GK gene (MODY2). Pancreas beta-cells generate 9cRA, and mouse 
      models of reduced beta-cell number, heterozygous Akita mice, and 
      streptozotocin-treated mice have reduced 9cRA. 9cRA is abnormally high in 
      glucose-intolerant mice, which have beta-cell hypertropy, including mice with 
      diet-induced obesity (DIO) and ob/ob and db/db mice. These data establish 9cRA as 
      a pancreas-specific autacoid with multiple mechanisms of action and provide 
      unique insight into GSIS.
FAU - Kane, Maureen A
AU  - Kane MA
AD  - Nutritional Science and Toxicology, College of Natural Resources, University of 
      California, Berkeley, CA 94720, USA.
FAU - Folias, Alexandra E
AU  - Folias AE
FAU - Pingitore, Attilio
AU  - Pingitore A
FAU - Perri, Mariarita
AU  - Perri M
FAU - Obrochta, Kristin M
AU  - Obrochta KM
FAU - Krois, Charles R
AU  - Krois CR
FAU - Cione, Erika
AU  - Cione E
FAU - Ryu, Joo Yeon
AU  - Ryu JY
FAU - Napoli, Joseph L
AU  - Napoli JL
LA  - eng
GR  - T32 DK061918/DK/NIDDK NIH HHS/United States
GR  - DK066924/DK/NIDDK NIH HHS/United States
GR  - R01 AA017927/AA/NIAAA NIH HHS/United States
GR  - F32 DK066924/DK/NIDDK NIH HHS/United States
GR  - R01 DK047839/DK/NIDDK NIH HHS/United States
GR  - DK47839/DK/NIDDK NIH HHS/United States
GR  - R01 DK090522/DK/NIDDK NIH HHS/United States
GR  - DK061918/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101129
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Autacoids)
RN  - 0 (Insulin)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Alitretinoin
MH  - Animals
MH  - Antineoplastic Agents/metabolism
MH  - Autacoids/*metabolism
MH  - Cell Line
MH  - Glucose/*pharmacology
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pancreas/cytology/*drug effects/*metabolism
MH  - Rats
MH  - Tretinoin/*metabolism
PMC - PMC3003056
COIS- The authors declare no conflict of interest.
EDAT- 2010/12/01 06:00
MHDA- 2011/05/13 06:00
PMCR- 2011/06/14
CRDT- 2010/12/01 06:00
PHST- 2010/12/01 06:00 [entrez]
PHST- 2010/12/01 06:00 [pubmed]
PHST- 2011/05/13 06:00 [medline]
PHST- 2011/06/14 00:00 [pmc-release]
AID - 1008859107 [pii]
AID - 201008859 [pii]
AID - 10.1073/pnas.1008859107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21884-9. doi: 
      10.1073/pnas.1008859107. Epub 2010 Nov 29.